Exploring the relationship between mild, repetitive traumatic brain injury and post-traumatic epilepsy: a review

Objective: The objective of this review is to explore the relationship between traumatic brain injury and the development of post-traumatic epilepsy. Background: According to the Centers for Disease Control and Prevention, traumatic brain injury (TBI) is considered a major public health problem in the United States. Each year, 2.53 million Americans, including 812,000 children, document a TBI-related emergency room visit. TBI is a disruption in the brain’s normal function, caused by a bump or blow to the head or by penetrating head injury. These injuries range in severity and can cause damage to one area of the brain, as in focal injuries, or multiple areas of the brain, as in diffuse injury. Mild TBI is often used synonymously with concussion, and these injuries comprise more than 90% of TBI cases. It has also been estimated that more than 40% of TBI-related hospitalizations result in long-term disability. Post-Traumatic Epilepsy (PTE) is defined as a recurrent seizure disorder secondary to trauma to the brain and has been described as one of the most devastating complications associated with TBI, as it can lead to neurodegenerative and neurocognitive symptoms. Most cases of PTE are resistant to existing anti-epileptic drugs, making treatment extremely difficult. Methods: The search engine PubMed was used. Search criteria included terms such as traumatic brain injury, epidemiology, post-traumatic epilepsy, mild TBI, sport-related concussion, neuroinflammation, astrocytes, gliosis, and biomarkers. Information from the Centers for Disease Control and Prevention and the American Association of Neurological Surgeons was also examined. Results were narrowed down to include literature from the years 2015-2021 and relevant literature from peer-reviewed journals was evaluated. Conclusions: Several pathophysiological mechanisms may be involved in the development of PTE. Elements of the neuroinflammatory response, including reactive astrogliosis and production of inflammatory compounds, may offer valuable insight into the development of PTE. Further research is needed to establish causal relationships, identify targets for therapeutic intervention, and ultimately prevent, manage, and treat PTE. Additionally, biomarkers may offer insight into secondary injury processes and provide a preventative advantage. Future studies should aim to qualitatively and quantitatively identify biomarkers specific to PTE development

Designing for Disability: Making Activities of Daily Living more Manageable through 3D Printing

Introduction: While there have been many innovations developed for those with physical disabilities in recent years, a multitude of unmet needs still remain. With the advent of new and affordable technologies such as 3D printing, it is now more possible than ever before to bring one’s ideas to life; from creating customized prosthetics to wheelchair attachments for water bottles and umbrellas, we are able to quickly realize potentials otherwise unlikely - and in turn, we have the capacity to make the activities of daily living more manageable for those with physical disabilities. Objectives: By personally hearing from individuals with physical disabilities about what challenges they face on a daily basis, it is possible to develop 3D printed items that can address their unmet needs. This work seeks to propose design(s) that can be conveniently created via an FDM 3D printer, in response to their expressed concerns. Methods: In accordance with the principles of appreciative inquiry, first-hand discussions with those having physical disabilities have allowed for some insight into a few of the current struggles they endure. Their stories have inspired the following proposed design(s) which can be 3D printed, with the hope that these developments can help them navigate the world we live in just a little bit easier. Results: Presented design(s) have been drafted in Autodesk Fusion 360 and initial prototypes are to be printed in ABS plastic with an Affinia FDM printer. Conclusions: 3D printing is an affordable, convenient, and promising means of developing items that can assist those with physical disabilities as they navigate our often inaccessible-world. While many changes require advocacy and intervention at the level of public policy, some impactful means of assistance can instead be constructed in this manner

Analysis of the Gut-Brain Axis in Aging: Implications in Alzheimer Disease

The gut microbiome is comprised of the shared genome of the trillions of microorganisms residing in the gastrointestinal ecosystem. The interaction between the host and its gut microbiome, the Gut-Bran Axis (GBA), is a complex relationship whose management could prove critical to preventing or treating not only various gut disorders, like irritable bowel syndrome (IBS) or behavioral health disorders such as general depression and anxiety, but also central nervous system (CNS) disorders, such as Alzheimer\u27s (AD) and Parkinson\u27s (PD) diseases. The purpose of this review is to summarize what is currently known about the gut microbiome, how it is connected to the development of disease pathology and to identify the bacterial and biochemical targets/pathways that should be the focus of future research. In identifying, exploring, and understanding the mechanisms behind the activity and propagation of the gut microbiome, this will provide us new insights that are likely to pave the way for increased novel therapeutic strategies

The Barriers that Deter the Geriatric Population From Receiving Healthcare

In the United States, the geriatric population is considered to include individuals that are 65 years or older. In 2016, there was an estimated 49.2 million elderly Americans (Roberts, Ogunwole, Blakeslee, & Rabe 2018). Since the advances of modern medicine are prospering, this number is expected to increase drastically. Furthermore, the geriatric population is projected to double, from 2010 to 2030, to 20% or 72 million Americans (Horton and Johnson 2010). Looking further into the future, the American geriatric population is expected to be 83.7 million in 2050 (Ortman, Velkoff, & Hogan 2014). In a 2016 Center for Disease Control and Prevention (CDC) report, the American geriatric population self-reported the highest percentage of “fair” or “poor” overall health (Center for Disease Control and Prevention 2018b). In response, the United States Department of Health and Human Services set up additional programs and resources to improve this rating; however, with the many health complications that older Americans face, there has been a surprising inconsistent quality of care for this population. The disparity becomes significant since many geriatric patients deal with chronic health complications. Previous studies show that there are both tangible and intangible factors as to why the geriatric population face issues with access to healthcare or the quality of care. This retrospective analysis looked at the different types of barriers for the geriatric population in the United States. This study investigated the barriers in rural settings, urban settings, and more specifically Philadelphia, where the medical field is expanding to better care for this population. Physicians’ behavior and attitude towards patients, “difficulty in getting to the doctor, the absence of services, lack of career progression opportunities for physicians, and the increased financial burden” are the many barriers, which geriatric patients face when trying to access quality healthcare (Douthit, Dwolatzky, & Biswas 2015). One might think tangible barriers, such as the cost of medical care, would be the major barrier facing this population. However, studies concluded that the perceived behavior and attitude of the physician is the most significant barrier that deters the geriatric population from wanting to receive medical care. Possible solutions to this issue include reform of healthcare policy and focusing on patient-centered care

The Efficacy of Applied Behavior Analysis on the Quality of Critical Life Skills in Autistic Youth

Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulties in social interaction, social communication, restricted and repetitive patterns of behavior, and interest or activities. As of 2013, ASD is no longer an individual entity but rather an umbrella term encompassing other distinctive developmental disorders. Signs and symptoms of ASD can appear anywhere from birth to three years of life. Various behavioral modalities exist for the treatment of ASD, which is considered to be the gold standard of care. One of the newest behavioral modalities is applied behavior analysis (ABA) therapy. The general purpose of ABA therapy is the application of techniques aimed at modifying behavior of social importance. In this context, it aims at establishing the link between particular behaviors and the environment, as opposed to solely modifying behavior. This is typically achieved through offering rewards for positive behavior and developing socially conventional substitutions for atypical behavior. The general consensus regarding the efficacy of ABA therapy in autistic youth is positive, particularly from the American Academy of Pediatrics. However, critics of the modality exist within the autistic community, with the majority of disparagement being rooted in an alleged link between ABA therapy and post-traumatic stress disorder (PTSD) as well as depression. Despite these denunciations, the overwhelming majority of behavioral researchers have found that ABA therapy is not only a legitimate form of behavioral therapy for autistic youth, but that those who receive early and intensive behavioral treatment have been shown to make extensive and prolonged gains in language, academic performance & adaptive ability

A Day in the Life of an Osteopathic Medical Student

During this past fall semester, in Tova Goldstein’s Introduction to Photography class, there was an assignment to create a photo essay. Anything that tells a story would be acceptable. Guidelines were provided that we were encouraged to follow but were not mandatory such as shooting a large group, head-shots, sequence of steps, and more. Since Tova is fortunate enough to have her father on staff at PCOM, It was thought to be fine to show a day in the life of an osteopathic medical student! On November 3, 2016, Tova Goldstein visited the campus to explore opportunities for her project. The camera used was a Canon EOS Rebel T5. Tova took many pictures of the library, a computer study area, the Osteopathic Manipulative Medicine (OMM) lab, Clinical Learning Assessment Center where simulations were conducted, and then the Anatomy Lab. This presentation follows a sequence from obtaining information in the library and a computer lab to learning skills necessary for a physician in OMM and simulation labs to exploring the anatomy to learn deep details of the body structure. Collectively, this photo essay represents one day in the life of an osteopathic medical student. ACKNOWLEDGEMENTS She appreciates the assistance of Dr. Denah Appelt, Dr. Arthur Sesso, Dr. Michael McGuiness, Dr. Donald Allison, Dr. Georges and the osteopathic medical students, and thanks them for giving her permission to complete her chosen assignment. Tova Goldstein is a third year undergraduate student at Kutztown University whose major is Graphics and Advertising Desig

Differential expression of E-cadherin, N-cadherin and beta-catenin in proximal and distal segments of the rat nephron.

BACKGROUND: The classical cadherins such as E- and N-cadherin are Ca(2+)-dependent cell adhesion molecules that play important roles in the development and maintenance of renal epithelial polarity. Recent studies have shown that a variety of cadherins are present in the kidney and are differentially expressed in various segments of the nephron. However, the interpretation of these findings has been complicated by the fact that the various studies focused on different panels of cadherins and utilized different species. Moreover, since only a few of the previous studies focused on the rat, information regarding the expression and localization of renal cadherins in this important species is lacking. In the present study, we have employed dual immunofluorescent labeling procedures that utilized specific antibodies against either E- or N-cadherin, along with antibodies that target markers for specific nephron segments, to characterize the patterns of cadherin expression in frozen sections of adult rat kidney. RESULTS: The results showed that N-cadherin is the predominant cadherin in the proximal tubule, but is essentially absent in other nephron segments. By contrast, E-cadherin is abundant in the distal tubule, collecting duct and most medullary segments, but is present only at very low levels in the proximal tubule. Additional results revealed different patterns of N-cadherin labeling along various segments of the proximal tubule. The S1 and S2 segments exhibit a fine threadlike pattern of labeling at the apical cell surface, whereas the S3 segment show intense labeling at the lateral cell-cell contacts. CONCLUSIONS: These results indicate that E- and N-cadherin are differentially expressed in the proximal and distal tubules of rat kidney and they raise the possibility that differences in cadherin expression and localization may contribute to the differences in the susceptibility of various nephron segments to renal pathology or nephrotoxic injury

Astrocytes Infected with Chlamydia pneumonia Alter Amyloid Processing Implicated in Alzheimer’s Disease

Alzheimer’s Disease (AD) is a chronic, progressive neurodegenerative disease whose pathogenesis centers around the abnormal processing of amyloid precursor protein (APP) by proteases, resulting in the formation of neuritic plaques composed of toxic, insoluble fragments of amyloid protein (Aβ), including Aβ1-40 and Aβ1-42. Previously, our laboratory identified Chlamydia pneumoniae (Cpn) in autopsied sporadic AD brains. Additionally, an infection based animal model was developed using BALB/c mice that were intranasally inoculated with Cpn, in which the deposition of amyloid was consistent with that observed in the human AD brain. These studies have led to the pathogen hypothesis of AD that implicates Cpn as a trigger for the cleavage of APP into Aβ1-40 and Aβ1-42. Objective: Several studies have demonstrated the presence of astrocytes surrounding neuritic plaques within the AD brain; therefore, we speculate that astrocytes may be specifically involved in the pathological processes leading to Aβ deposition. This investigation addresses if an in vitro Cpn infection of human astrocytes affects processing of the ß amyloid precursor protein (ßAPP) and the enzyme ß APP cleaving enzyme-1 (BACE1), a type 1 transmembrane aspartyl protease directly involved in the processing of APP to Aβ and implicated in numerous neurodegenerative diseases, such as traumatic brain injury. Methods: Human astrocytes (CCF-STTG1) were infected in vitro with the respiratory strain AR39 Cpn (MOI=1). Analysis of protein levels for Aβ and the enzyme BACE1 post-infection was detected by immunocytochemistry and captured with the Olympus Confocal FV1000 microscope. Results: Amyloid processing in infected astrocytes was altered relative to that of uninfected astrocytes. BACE1 immunolabeling appeared more diffuse in the infected astrocytes as compared to membrane-localized BACE1 in the uninfected astrocytes. Conclusions: Neurons have been presumed to be the primary source of beta-amyloid peptides in AD brains; however, when astrocytes are activated, as occurs during infection with Cpn, astrocytic beta-amyloid generation may contribute to amyloid plaque formation. These data imply that infection of human astrocytes with Cpn affects the processing of ßAPP through altering the localization of BACE1 protein from the membrane to the cytoplasm. These data suggest an activation of BACE1 in the processing of amyloid by astrocytes as a major contributor to the neurotoxic amyloid deposition linked to pathology observed in AD

Editorial: Infection, inflammation, and neurodegeneration: A critical path to Alzheimer\u27s disease, Volume II.

No abstract availabl

Astrocytes Infected with Chlamydia Pneumoniae Demonstrate Altered Expression and Activity of Secretases Involved in the Generation of Β-amyloid Found in Alzheimer Disease

BACKGROUND: Epidemiologic studies strongly suggest that the pathophysiology of late-onset Alzheimer disease (AD) versus early-onset AD has environmental rather than genetic causes, thus revealing potentially novel therapeutic targets to limit disease progression. Several studies supporting the pathogen hypothesis of AD demonstrate a strong association between pathogens and the production of β-amyloid, the pathologic hallmark of AD. Although the mechanism of pathogen-induced neurodegeneration of AD remains unclear, astrocytes, a key player of the CNS innate immune response and producer/metabolizer of β-amyloid, have been implicated. We hypothesized that Chlamydia pneumoniae infection of human astrocytes alters the expression of the amyloid precursor protein (APP)-processing secretases, ADAM10, BACE1, and PSEN1, to promote β-amyloid formation. Utilizing immunofluorescent microscopy, molecular, and biochemical approaches, these studies explore the role of an intracellular respiratory pathogen, Chlamydia pneumoniae, as an environmental trigger for AD pathology. Human astrocytoma cells in vitro were infected with Chlamydia pneumoniae over the course of 6-72 h. The gene and protein expression, as well as the enzymatic activity of non-amyloidogenic (ADAM10), and pro-amyloidogenic (BACE1 and PSEN1) secretases were qualitatively and quantitatively assessed. In addition, the formation of toxic amyloid products as an outcome of pro-amyloidogenic APP processing was evaluated through various modalities. RESULTS: Chlamydia pneumoniae infection of human astrocytoma cells promoted the transcriptional upregulation of numerous genes implicated in host neuroinflammation, lipid homeostasis, microtubule function, and APP processing. Relative to that of uninfected astrocytes, BACE1 and PSEN1 protein levels were enhanced by nearly twofold at 48-72 h post-Chlamydia pneumoniae infection. The processing of APP in Chlamydia pneumoniae-infected astrocytes favors the pro-amyloidogenic pathway, as demonstrated by an increase in enzymatic activity of BACE1, while that of ADAM10 was decreased. Fluorescence intensity of β-amyloid and ELISA-quantified levels of soluble-APP by products revealed temporally similar increases, confirming a BACE1/PSEN1-mediated processing of APP. CONCLUSIONS: Our findings suggest that Chlamydia pneumoniae infection of human astrocytes promotes the pro-amyloidogenic pathway of APP processing through the upregulation of expression and activity of β-secretase, upregulated expression of γ-secretase, and decreased activity of α-secretase. These effects of astrocyte infection provide evidence for a direct link between Chlamydia pneumoniae and AD pathology